InfluenzaPhase 3NCT03900988
Intravenous N-acetylcysteine and Oseltamivir Versus Oseltamivir in Adults Hospitalized With Influenza and Pneumonia
A Phase 3 study testing N-acetyl cysteine and 5% Dextrose in people with Influenza, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Seasonal influenza epidemics are important causes of morbidity and mortality. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Influenza
- What is being tested?
- N-acetyl cysteine and 5% Dextrose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteHong Kong
- Study dates
- 8 May 2023to 31 Dec 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- influenza A and B virus infections confirmed by polymerase chain reaction (PCR) and/or immunofluorescence assays,
- hospitalized for the management of severe manifestations of influenza,
- initiation of oseltamivir,
- clinical evidence of lower respiratory tract infection (e.g. shortness of breath, tachypnea, oxygen desaturation <93% on room air, crepitations on auscultation, infiltrations or consolidations on chest radiograph)
- written informed consent (by the subjects, or from their next of kin if the subjects are unable to provide written consent at the time of enrollment)
Who cannot join
- use of immunosuppressants (e.g. post-chemotherapy, post-transplant, autoimmune diseases) other than systemic corticosteroids
- known immuno-compromised conditions (e.g. active haematological malignancies, HIV/AIDS patients who are on antiretroviral therapy and CD4 cell count < 200),
- pregnancy
- lactation,
- end-stage renal failure
- hepatic failure
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- cardiac failure
- patients on anticoagulation (except prophylactic dose of low molecular weight heparin),
- patients with scheduled major surgery within 2 weeks (NAC may affect blood clotting),
- patients who have received macrolide antibiotics and NSAID for 1 week prior to enrolment due to their immuno-modulating effects.
- Use of investigational anti-influenza antivirals and blood products
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong
Ken Ka Pang Chan, 3505 3532, chankapang@cuhk.edu.hk
About this study
Official title: A Randomized, Double Blind, Placebo Controlled Trial of Intravenous N-acetylcysteine and Oseltamivir Versus Intravenous 5% Dextrose and Oseltamivir in Adults Hospitalized With Influenza Complicated by Lower Respiratory Tract Infection.
Seasonal influenza epidemics are important causes of morbidity and mortality. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza. Early therapy with a neuraminidase inhibitor (NAI) is associated with better outcome in patients hospitalized with influenza, but significant mortality occurs despite use of antivirals. N-acetylcysteine (NAC) is a modified form of the amino acid cysteine, with anti-oxidant properties. NAC was shown to inhibit the production of pro-inflammatory molecules in lung epithelial cells infected with influenza viruses. Previous case report showed that high dose NAC, administered as continuous intravenous infusion, was effective and safe in improving the clinical outcomes. We aim to perform a randomized controlled trial to evaluate the therapeutic role of adjunctive NAC in the clinical management of patients with influenza complicated by lower respiratory tract involvement and abnormal respiratory status. Such information when available may reveal the potential of NAC for optimization of management of severe influenza, and provide important insights into future adjunctive therapy research.
- Conditions
- Influenza
- Being tested
- N-acetyl cysteine, 5% Dextrose
- Keywords
- respiratory, mortality, cytokines, chemokines, N-acetylcysteine (NAC)
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl cysteineDrug
N-acetyl cysteine will be administered at 100 mg/kg daily as a continuous IV infusion (in 1000ml of 5% dextrose) over 24 hrs and oseltamivir 75 mg bid orally for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.
5% DextroseDrug
5% dextrose 1 liter given over 24 hrs and oral oseltamivir 75 mg bid for 5 days. Extension of dosing to 10 days for oseltamivir and the study drug is allowed if there is slow recovery, lack of improvement, or deterioration.
| Study group | Role | What they receive |
|---|---|---|
| intravenous N-acetylcysteine (NAC) and oseltamivir | Active comparator | Not described Receives: Drug: N-acetyl cysteine |
| intravenous 5% dextrose and oseltamivir | Placebo comparator | Not described Receives: Drug: 5% Dextrose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalization of respiratory status in day
oxygen saturation more than 93% or respiratory rate lower than 20/min on room air
Measured: 28 days
Secondary outcomes (15)
viral ribonucleic acid (RNA) in copies per milliliter
All serially collected samples will be subjected to viral ribonucleic acid (RNA) quantification using quantitative reverse transcription PCR (qRTPCR) targeting the matrix (M)-gene ('viral load')
Measured: 28 days
Interleukin 6 in pg/ml
Measured: 10 days
interleukin-8 in pg/ml
Measured: 10 days
interleukin 17 in pg/ml
Measured: 10 days
Chemokine ligand 9 (CxCL9/MIG) in pg/ml
Measured: 10 days
Soluble tumour necrosis factor receptor-1 (sTNFR-1) in pg/ml
Measured: 10 days
interleukin 18 in pg/ml
Measured: 10 days
CRP in mg/L
Measured: 10 days
phospho-p38 and phospho-ERK (activated MAPKs) in mean fluorescence intensity(MFI)
Measured: 10 days
phospho-inhibitor kB/IkB (NF-kB) in mean fluorescence intensity(MFI)
Measured: 10 days
resolution of symptoms in days
A standard questionnaire will be used to collect baseline and serial clinical data. These include clinical manifestations/complications, symptom severity score, vital signs (e.g. temperature, respiratory rate, oxygen saturation), fever duration, requirements for supplemental oxygen therapy and invasive/non-invasive ventilation, duration of hospitalization, death, and occurrence of adverse events.
Measured: 28 days
ICU admission in days
Measured: 28 days
mortality in days
Measured: 28 days
Incidence of Treatment-Emergent Adverse Events in numbers
Measured: 28 days
a six step ordinal scale of clinical status
death, in ICU, ongoing hospitalisation on oxygen, hospital stay not on oxygen, discharged but not returned to normal activities, or discharged and returned to normal activities
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2019
- Study start8 May 2023
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof David Shu Cheong Hui, Chinese University of Hong Kong
- Investigators
- David SC Hui, MD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03900988
- Sponsor's protocol ID
- NAC Influenza/Hui/2019
- Status last verified
- Oct 2026
- First submitted
- 31 Mar 2019
- Last updated
- 20 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No